.DELTA..sup.9 -Tetrahydrocannabinol [THC], depicted in Formula I under alternate numbering systems, is the major psychoactive constituent of marijuana. ##STR1## In addition to mood-altering effects, THC has been reported to exhibit other activities, some of which may have therapeutic value. The potential therapeutic value of THC has led to a search for related compounds which, while devoid of psychoactive effects, retain the activities of potential medicinal value.
Previous work with .DELTA..sup.8 -Tetrahydrocannabinol [(3R,4R) 6a,7,10,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol, hereinafter referred to as .DELTA..sup.8 -THC], which is depicted in Formula II below, has indicated that certain derivatives of this compound depicted in Formula II below, may prove clinically useful. The 11-carboxy derivative of .DELTA..sup.8 -THC [.DELTA..sup.8 -THC-11-oic acid] has been reported to be a non-psychoactive, potent antagonist to endogenous platelet activating factor and, thus, a useful treatment for PAF-induced disorders, such as asthma, systemic anaphylaxis, and septic shock. (U.S. Pat. No. 4,973,603, issued to the present inventor). Another derivative, (3S,4S)-11-hydroxy-.DELTA..sup.8 -THC-1',1' dimethylheptyl essentially free of the (3R,4R) form, has been reported to possess analgesic and anti-emetic activities. (U.S. Pat. No. 4,876,276).
U.S. Pat. No. 4,847,290, issued to the present inventor, discloses a method of relieving pain in mammals by administering an effective analgesic amount of .DELTA..sup.9 -THC-11-oic acid or an analog thereof. These THC derivatives are disclosed to be non-psychoactive metabolites.
U.S. Pat. No. 5,338,753, also issued to the present inventor, discloses (3R,4R)-.DELTA..sup.8 -Tetrahydrocannabinol-11-oic acid derivatives having Formula II below: ##STR2## wherein R.sup.1 is a hydrogen atom, --COCH.sub.3 or --COCH.sub.2 CH.sub.3 ; R.sup.2 is a straight chain or branched C.sub.5 -C.sub.12 alkyl, which may have a terminal aromatic ring; a group --(CH.sub.2).sub.m --O--R.sup.3, wherein m is an integer from 0 to 7 and R.sup.3 is a straight chain or branched alkyl group containing from 1 to 12 carbon atoms, which may have a terminal aromatic ring; or a group CH--(CH.sub.3)--(CH.sub.2).sub.n --O--R.sup.4, wherein n is an integer from 0 to 7 and R.sup.4 is a straight chain or branched alkyl containing from 1 to 12 carbon atoms, which may have a terminal aromatic ring. These .DELTA..sup.8 -THC-11-oic acid derivatives are also discussed in an article by Sumner H. Burstein, et al., entitled "Synthetic Nonpsychotropic Cannabinoids with Potent Antiinflammatory, Analgesic, and Leukocyte Antiadhesion Activities." [J. Medicinal Chem., 35(17):3135-3136 (1992).
It is desired, however, to obtain compounds, pharmaceutical compositions, and methods of treatment using compounds substantially devoid of psychoactive effect and with improved therapeutic effects compared to those achieved by conventional .DELTA..sup.8 -THC-11-oic acid derivatives, such as those described above. The present invention advantageously affords such compounds, pharmaceutical compositions, and methods of treatment using the compounds and compositions.